Is STK4 p.Arg231= (c.693G>A) pathogenic?

STK4 p.Arg231= (c.693G>A) is classified Uncertain significance in STK4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). Absent from gnomAD v4.1; Associated with combined immunodeficiency due to STK4 deficiency.

What condition is associated with STK4 p.Arg231= (c.693G>A)?

STK4 p.Arg231= (c.693G>A) is associated with combined immunodeficiency due to STK4 deficiency (ClinVar).

How common is STK4 p.Arg231= (c.693G>A) in the general population?

STK4 p.Arg231= (c.693G>A) is absent from gnomAD v4.1 (gnomAD).

STK4 p.Arg231=

Q: How is Combined immunodeficiency due to STK4 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.693G>A · VCV3704673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,902)

Conditions

combined immunodeficiency due to STK4 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.30	loss · gain 0.05 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.1	GERP 0.94, phastCons 1
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,607,902). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: STK4
Protein: p.Arg231=
Coding: c.693G>A
MANE Select: NM_006282
Type: single nucleotide variant
Location: chr20:44995257 (GRCh38)
Gene constraint: LOEUF 0.6 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 76.45 · 16 PDB
Residue 231: the protein kinase domain; an α-helix

Full STK4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to STK4 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to STK4 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

STK4 p.Arg115Ter Pathogenic/Likely pathogenic ★★ same condition
STK4 p.Arg117Ter Pathogenic ★★ same condition
STK4 p.Arg148Ter Pathogenic ★★ same condition
STK4 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
STK4 p.Ala391Val Uncertain significance ★★ ⚠ same condition
STK4 p.Ala479Ser Uncertain significance ★★ ⚠ same condition
STK4 p.Arg310Gln Uncertain significance ★★ ⚠ same condition
STK4 p.Arg310Pro Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/stk4-p-arg231 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown